What screening questions should I ask before prescribing raloxifene (Selective Estrogen Receptor Modulator) to a CHEK2 (Checkpoint Kinase 2) mutation carrier with normal lipid profile, normal renal (kidney) function, and normal liver function?

Screening Questions Before Prescribing Raloxifene to a CHEK2 Mutation Carrier

Before prescribing raloxifene to a CHEK2 mutation carrier, you should conduct a thorough assessment for venous thromboembolism risk factors, cardiovascular disease, stroke history, and complete a detailed family cancer history, as these factors significantly impact morbidity and mortality outcomes with this medication. 1, 2

Venous Thromboembolism (VTE) Risk Assessment

• History of previous blood clots in legs, lungs, or eyes
• Family history of blood clots
• Prolonged immobility (recent surgery, long travel plans)
• Smoking status
• Obesity
• Age (risk increases with age)

Cardiovascular Risk Assessment

• History of heart attack or stroke
• History of mini-stroke (TIA)
• Presence of irregular heartbeat (especially atrial fibrillation)
• Hypertension status
• Diabetes status
• Smoking status

Detailed Cancer History

• Personal history of breast cancer (raloxifene has not been fully studied in women with a history of breast cancer) 2
• Family history of breast cancer (maternal and paternal sides)
• Age of breast cancer onset in family members
• Other cancers in the family (especially colorectal cancer, given CHEK2 association) 1
• Consider using CanRisk assessment tool to estimate breast cancer risk 1

Medication History

• Current medications, particularly:
  • Warfarin or other coumarin blood thinners (may need INR monitoring) 2
  • Cholestyramine (reduces raloxifene absorption by 60%) 2
  • Estrogens (should not be taken with raloxifene) 2
  • Ampicillin/amoxicillin (may reduce raloxifene concentrations) 2

Reproductive History

• Confirm postmenopausal status (raloxifene is only for postmenopausal women) 2
• Pregnancy status (contraindicated in pregnancy) 2
• Breastfeeding status (contraindicated during breastfeeding) 2

Organ Function Assessment

You've already checked:

• Liver function (normal) - good, as hepatic impairment increases raloxifene concentrations by 150% 2
• Kidney function (normal) - good, as renal impairment increases raloxifene concentrations by 122% 2
• Lipid profile (normal) - good, as raloxifene can affect lipid metabolism 2, 3

Patient Education Points

• Discuss the need to avoid prolonged immobility
• Review warning signs of VTE that require immediate medical attention:
  • Leg pain or warmth in lower leg
  • Swelling of legs, hands, or feet
  • Sudden chest pain or shortness of breath
  • Coughing up blood
  • Sudden vision changes 2
• Explain that raloxifene may reduce invasive breast cancer risk by 76% over 3 years 4
• Discuss that VTE risk is increased approximately 3-fold with raloxifene 4, 5

Special Considerations for CHEK2 Carriers

• CHEK2 carriers have an increased baseline risk of breast cancer that varies by specific variant and family history 1
• Consider recommending genetic testing for close female relatives, particularly sisters 1
• Discuss that country-specific surveillance guidelines should be followed for breast cancer screening 1
• In the absence of family history of colorectal cancer, follow population-based guidelines for colonoscopy surveillance 1

Remember that while raloxifene can reduce breast cancer risk, it also carries risks of venous thromboembolism and potentially fatal stroke that must be carefully weighed against the benefits in each individual CHEK2 mutation carrier 1, 2.